Kronos早期雌激素预防研究(KEEPS)是一项随机研究,双盲,安慰剂对照试验旨在确定激素治疗(更年期激素治疗[MHTs])对最近更年期女性颈动脉内膜-中层厚度(CIMT)进展的影响。参与者从绝经后不到3年,没有明显的心血管疾病(CVD)的历史,定义为无临床CVD事件和冠状动脉钙<50Agatston单位,口服结合马雌激素(0.45毫克/天)或经皮17β-雌二醇(50微克/天),均使用黄体酮(200毫克/天,持续12天/月),或安慰剂药丸和贴片4年。尽管MHT并没有降低CIMT中与年龄相关的增加,KEEPS提供了有关MHT效应的其他重要见解。与安慰剂相比,MHTs降低了更年期症状的严重程度并维持了骨密度,但在情绪/焦虑方面的功效不同,睡眠,性功能,和β-淀粉样蛋白在大脑中的沉积。此外,代谢和摄取雌激素酶的遗传变异影响了MHT缓解症状的某些方面的功效。KEEPS为MHT在临床实践中的使用提供了重要信息,包括类型,剂量,以及绝经后最近MHT的分娩方式,以及激素代谢中的遗传变异如何影响MHT对特定结局的疗效。
The Kronos Early Estrogen Prevention
Study (KEEPS) was a randomized, double-blind, placebo-controlled
trial designed to determine the effects of hormone treatments (menopausal hormone treatments [MHTs]) on the progression of carotid intima-medial thickness (CIMT) in recently menopausal women. Participants less than 3 years from menopause and without a history of overt cardiovascular disease (CVD), defined as no clinical CVD events and coronary artery calcium < 50 Agatston units, received either oral conjugated equine estrogens (0.45 mg/day) or transdermal 17β-estradiol (50 µg/day), both with progesterone (200 mg/day for 12 days/month), or placebo pills and patches for 4 years. Although MHT did not decrease the age-related increase in CIMT, KEEPS provided other important insights about MHT effects. Both MHTs versus placebo reduced the severity of menopausal symptoms and maintained bone density, but differed in efficacy regarding mood/anxiety, sleep, sexual function, and deposition of β-amyloid in the brain. Additionally, genetic variants in enzymes for metabolism and uptake of estrogen affected the efficacy of MHT for some aspects of symptom relief. KEEPS provides important information for use of MHT in clinical practice, including type, dose, and mode of delivery of MHT recently after menopause, and how genetic variants in hormone metabolism may affect MHT efficacy on specific outcomes.